A variety of synthetic resinous materials have been used or proposed to be used for the fabrication of articles to be employed in contact with blood and/or other body fluids. However, the only material fully accepted in the United States at the present time for use in blood tubing and blood bags is polyvinyl chloride (PVC) plasticized with dioctyl phthallate (DOP)--also known as di-2-ethylhexyl phthallate (DEHP). Even the plasticized PVC leaves something to be desired. That is, leaching of the DOP by blood occurs, with the result that DOP accumulates in the body tissues and vital organs of patients repeatedly subjected to treatments such as blood dialysis. Clinical testing of a PVC plasticized with a different ester--trioctyl mellitate--was FDA-approved but has been at least temporarily discontinued. An olefin terpolymer material has also received approval for clinical testing but remains to be proven out.
Several types of polyurethanes have been proposed as bio and hemocompatible materials. U.S. Pat. No. 4,062,834 (1977) teaches the suitability for use as blood bags of certain melt-extrudable, thermoplastic, polytetramethylene ether polyurethane-urea elastomers (having Shore A hardness values of 70-87). These polymers are made by preparing a pre-polymer (having an isocyanate index of 1.3/1 to 1.7/1) from a tetramethylene ether glycol and 4,4'-diphenyl methane diisocyanate and then extending it with water. However, it is now known that aryl urethanes tend to produce carcinogenic aromatic amines when subjected to conditions favorable to hydrolysis, such as those prevailing during steam sterilization.
U.S. Pat. No. 4,447,590 (May 1984) discloses, as suitable blood bag materials, certain extrudable polyurethanes prepared, by a "one-shot" process, from tetramethylene glycol, aliphatic diisocyanates and 1,4-butane diol (as a chain extender). The patent teaches that polytetramethylene glycol is the only polyol found to produce a polyurethane which not only has the requisite hemocompatibility but also has other properties--such as hydrolytic stability and non-toxicity--required for candidate blood bag materials.
U.S. Pat. No. 4,460,365 (July 1984) teaches that, to be suitable for use as blood bags, polyurethanes must have Shore A hardness values of about 60-85 and that whether or not a polyurethane meeting this requirement is otherwise suitable for blood bag use can be determined by known test methods. The chemical composition of the only specific polyurethane purported to meet blood bag requirements is not given.
U.S. Pat. No. 4,465,480 is directed to segmented, polyether urethane ureas of reduced thrombogenicity. These urethanes are made by using aliphatic or cycloaliphatic diamines to extend urethane prepolymers made from polyoxyalkylene diols and diisocyanates--such as 4,4'-diphenylmethane diisocyanate, for example. They are said to avoid the generation of aromatic amines consequent upon using water as a chain extender (as in the +590 patent discussed above). However, this of course would not ensure non-hydrolysis during steam sterilization. The disclosure in the patent suggests strongly that the subject polymers must be prepared and processed as solutions in solvents such as dimethyl formamide, i.e., are not extrudable.
The latter patents are believed to constitute the nearest prior art to the present invention. It does not appear that any of the dissolved polymers--or any polymer that could reasonably be contended to be suggested by these patents--meets the following requirements to the extent desirable for a second generation blood bag/blood tubing material.
To be suitable as a replacement for PVC/DOP, a candidate material should at least: have mechanical and biocompatibility properties comparable to those of PVC, be non-toxic, be not substantially more expensive than PVC, contain nothing which will be leached out by blood (or is not known to be innocuous), be capable of being tightly bonded at joints and connections, retain its mechanical integrity and performance at body temperatures (about 38.degree. C.), not fail in mechanical handling, be hydrolytically stable at steam sterilization temperatures and not be prone to kinking. Desirably, such a material is both soft and tough, is transparent, has a relatively high permeability to O.sub.2 and CO.sub.2, retains its room temperature mechanical properties after being chilled to low temperatures, can be thermoformed without decomposing or becoming thermoset, has an acceptable "feel" to those people (nurses, for example) who must handle the material frequently and affords a longer "shelf life" container for stored blood or blood components. The difficulty of finding a material--polyurethane or otherwise--which can largely satisfy the foregoing requirements should be apparent.